ROAMING: SOLUTION STRUCTURE OF PNA AND DNA DOUBLE-HELICES WITH AND WITHOUT META

漫游：带或不带 Meta 的 PNA 和 DNA 双螺旋的解结构

• 批准号: 8171860
• 负责人: MARCELA MADRID
• 金额: $ 0.11万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8171860
• 关键词: Anti-HIV Agents; Binding; Charge; Collaborations; Complex; Computer Retrieval of Information on Scientific Projects Database; Electron Transport; Electronics; Ensure; Funding; Generations; Goals; Grant; HIV-1 Reverse Transcriptase; Institution; Laboratories; Metals; Methods; Modification; Molecular; Mutation; Peptide Nucleic Acids; Pharmaceutical Preparations; Progress Reports; RNA-Directed DNA Polymerase; Research; Research Personnel; Resources; Solutions; Solvents; Source; Structure; System; United States National Institutes of Health; base; design; flexibility; mutant; research study

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This proposal consists of two projects: Project 1. PNA solution structure. The objectives of this proposal are to characterize the structure and dynamics of PNA/PNA and DNA/DNA double helices in solution, with different metal substitutions. The obtained structures will be used as input to semi-empirical and ab initio electron transfer (ET) studies, in order to study the effect of sequence, structure, flexibility, solvent and charge on ET. Our long-term goal is to design and synthesize molecular systems based on metal-peptide nucleic acids (metal-PNA) duplexes, which allow the precise control of electronic flow. This project is a fruitful collaboration with Prof. Catalina Achim, who synthesizes metal-containing PNA, Prof. David Waldeck and Eric Borguet, who conduct electron transfer experiments, and Prof. David Beratan, who will use ab-initio and semi-empirical methods to calculate electron transfer rates. Project 2. Mutant RT-NNRTI complexes. The long term goal of our HIV-1 reverse transcriptase (RT) research is to design new anti-AIDS drugs, more effective against wild-type and mutant RT. We have recently completed a study of the interactions of several drugs (including the latest generation, more effective, DAPYs) in the binding pocket of wild-type RT (as detailed in the Progress Report). In order to propose modifications to these drugs, we need to ensure that our conclusions are also valid in the presence of mutant RT. The proposed modifications should, then, be effective against both wild-type and commonly occurring mutations. The objectives of the proposed research are to understand the interactions with mutant RT Lys103Asn. The proposed drug derivatives will be synthesized in the laboratory of our collaborator, Prof. Brin.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 该建议由两个项目组成：项目1。PNA解决方案结构。这 该建议的目标是表征PNA/PNA的结构和动力学 溶液中的DNA/DNA双螺旋，具有不同的金属取代。这 获得的结构将用作半经验和依从电子的输入 转移（ET）研究，以研究序列，结构，灵活性的影响 溶剂并在ET上充电。我们的长期目标是设计和合成分子 基于金属肽核酸（金属-PNA）双链体的系统，该系统允许 电子流的精确控制。这个项目是与教授的富有成效的合作。 Catalina Achim，合成了含金属PNA的PNA，David Waldeck教授和Eric教授 进行电子转移实验的Borguet和David Beratan教授 将使用Ab-Initio和半经验方法来计算电子传递速率。 项目2。突变的RT-NNRTI复合物。我们的HIV-1反向的长期目标 转录酶（RT）研究是设计新的抗AIDS药物，更有效地反对 野生型和突变体RT。我们最近完成了一项研究 在结合中 野生型RT的口袋（如进度报告中所述）。为了提出 修改这些药物，我们需要确保我们的结论也有效 在存在突变rt的情况下。然后，提议的修改应有效 反对野生型和通常发生的突变。目标的目标 拟议的研究是了解与突变体RT Lys103ASN的相互作用。 拟议的药物衍生物将在我们的实验室中合成 合作者布林教授。